The human body is approximately 80% water; thus, it is advantageous to administer aqueous solutions of drugs to patients. However, not all compounds or drugs are easy to dissolve in water and often this is due to their poor solubility. Some compounds are slightly water soluble and others are not water soluble at all. Often this lack of solubility is compounded by further difficulties in forming a solution due to the physical nature of the materials for example their being viscous, glue-like or heat sensitive. Compounds that are not water soluble or slightly soluble may be soluble in organic solvents. Solutions of these compounds in organic solvents, however, may not be convenient for a variety of reasons. For example, regulatory authorities may limit the amount of organic solvents within a formulation to be administered to patients, or the organic solvents may be toxic. Therefore, while the preparation of aqueous solutions or suspensions of difficult to dissolve in water compounds is important in the field of drug delivery, many active pharmaceutical ingredients may not be available as solutions because they are water insoluble compounds. An example of a difficult to dissolve in water drug that must be solubilized prior to administration is latanoprost, which is used in ophthalmic solutions.
Traditionally, difficult-to-dissolve-in-water compounds that were intended to be formulated as dispersions or solutions were heated together with water to increase dissolution and facilitate solubility. A compound to be dissolved and water were often mixed and this mixture then heated to promote dissolution. After cooling the mixture to the desired temperature a solution or a dispersion of the substance in saturated solution could be obtained. A saturated solution could be obtained if any undissolved material was removed. This method, however, is ineffective where the compound to be dissolved is viscous and glue-like or heat sensitive. Viscous substances often stick to the walls of the vessel used to dissolve it or may agglomerate during cooling. For at least these reasons, solutions of difficult to dissolve compounds often can not even reach the theoretically possible concentrations and may even have difficulty being well-dispersed throughout the solution. Heating a slightly insoluble or insoluble compound is also inappropriate where the compound to be dissolved degrades upon heating. Moreover, this method is ineffective where the solubility of the compound to be dissolved is only slightly affected by an increase in temperature or not at all.
Therefore, the present invention addresses the deficiencies of the prior art. The invention encompasses methods for preparing suspensions or dispersions or aqueous solutions of difficult to dissolve in water or insoluble in water compounds, which can be applied to a variety of compounds without requiring heating to promote dissolution.